on the long-term efficiency and safety of biosimilars.
Because different manufacturing and purification
processes, and even distinct storage conditions
and distribution chains, make it almost impossible
to replicate the reference molecules, there are
currently concerns regarding the structure, purity,
and immunogenicity of the biosimilars. In addition,
different biosimilars for the same reference product
may present varying features and may not be
interchangeable. Despite the much anticipated
reduced healthcare costs associated with the use
of these molecules, which partially result from
the less extensive clinical development program
required to support product registration with the
regulatory authorities (evaluation of the similarity of
physicochemical, preclinical, and clinical data only),
biosimilar products may impact clinical practice and
patients in other ways. 2,3
Immunogenicity, thought to be a function of
a molecule’s physicochemical features, is a key
safety item from the regulatory point of view and
can be determined using in vitro (recognition and
binding assays with an array of antibodies against
the drug) and in vivo (cross-reactivity assay of
anti-drug antibodies isolated from treated patients)
methods. However, negative results in vitro may
not necessarily exclude immunogenic responses in
actual patients, and the immunogenicity might not
be comparable across studies due to differences in
methodologies, patient populations, prior exposure
to the reference product, concomitant drug use, and
the disease itself. For these reasons, immunogenicity
testing is a requirement in safety evaluations
as well as in post-marketing pharmacovigilance
programmes. 2,4
Clinicians must also be aware of how biosimilars
can affect patient adherence to treatment so that
potential issues can be addressed early on, before
any switch from a branded drug to its copy (in
particular how patients view these replacement
drugs in terms of potency and efficacy). 1 Many
factors are known to contribute to poor adherence,
including difficulties administering a drug, and
inconvenient, complex, and strict regimens.
However, patients’ attitudes towards medications
can also negatively impact the way they feel
about their new treatment regimens (for example,
uncertainty about the quality of the replacement
drug, fear of side effects, difficulties using a new
delivery system). 5
Educational initiatives focusing on the science
behind the manufacturing process and on the
available clinical experience with biosimilars
are therefore needed and can ultimately lead to
improved treatment plans, and subsequently clinical
outcomes, for patients together with improved
treatment adherence. 3
Increased
awareness of
these drugs, how
they are
developed, and
the current
regulatory
framework, can
play a significant
role in increasing
confidence
regarding their
use, not only for
clinicians but also
for patients
Pharmacists
As for clinicians, pharmacists need to be aware of
the potential benefits and concerns of biosimilars
because they are likely to see increasingly higher
numbers of prescriptions for these drugs in the
next years as the patents and exclusivity periods for
several biologics expire, hence the need to be able to
provide recommendations regarding optimal use for
patients. 1
This is of particular relevance in countries such
as the USA, where pharmacists are allowed to fill a
prescription with the brand drug or a replacement
without consulting the physician or the patient. In
some countries, insurance plans or governmental
directives may even mandate a switch to a biosimilar
whenever possible in order to reduce the burden
to healthcare systems. However, switching from
branded drugs to biosimilars has been reported to
affect dosing accuracy and adherence in some cases,
resulting in dosing errors or treatment lapses. 5
Pharmacists should be aware that questions about
interchangeability (the practice of substituting one
drug for another with the same clinical effects under
similar conditions by the prescriber or with his/her
agreement), switching (the practice of substituting
one drug for another with the same therapeutic
intent), and automatic substitution (the practice of
substituting one drug for another interchangeable
drug at the pharmacy level without consulting the
prescriber), as defined in the EU, still persist and
that these practices are not consistent between
countries. 4
Switching and substitution can in fact constitute
a cause of anxiety for patients who have doubts
about the efficacy and safety of biosimilars and
who may associate unrelated, undesirable events
with the new regimen. In addition, nomenclature
and traceability are particularly important for
pharmacists to facilitate the identification of
the active ingredient, and pharmacovigilance
programmes should distinguish between the
brand names of the biosimilar and reference drug,
including batch manufacturing information. 4
Patients
The main advantage of biosimilars is the potential
to provide similar clinical benefits with cost savings,
thereby allowing more patients to have access to
treatments that might otherwise be a prohibitive
expense in the long term, with limited availability
and accessibility due to restrictions in insurance and
public payer coverage, limited reimbursement, and
high out-of-pocket costs. Inadequate insurance
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